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Project

The impact of recurrent chromosomal abnormalities on growth advantage and differentiation capacity of human pluripotent stem cells (FWOTM1016)

Human pluripotent stem cells (hPSCs) can differentiate into any cell type of the adult human body and they hold a great promise in transplantation and regenerative medicine as well as in in vitro modeling of development and disease. hPSC cultures tend to acquire chromosomal abnormalities which provide them with a growth advantage. Currently, little is known on how genetic abnormalities affect the differentiation of the cells. In this project, we will elucidate whether the recurrent chromosomal changes identified in undifferentiated hPSC retain their selective advantage during differentiation and if they impact the quality of the differentiated progeny. We will mimic culture mosaicism by mixing fluorescently labelled pairs of hPSC lines with and without a chromosomal abnormality, and differentiate them to progenitor and mature cell types. With flow cytometry and single cell RNA sequencing we will study culture take-over and differentiation impairment to all 3 germ layers. Our results will represent the first information on how mosaic cultures can affect the end population of differentiated cells and will be the steppingstone to design assays for early detection of aneuploidies that are relevant for a specific cell type, which is essential to the transition of hPSC-derived cell types to a clinical setting. Future research will make use of the transcriptomic data of this project to investigate the mechanisms behind differentiation impairment in genetically unbalanced cells.
Date:1 Nov 2020 →  Today
Keywords:Human pluripotent stem cells, genetic abnormalities, growth advantage, differentiation impairment
Disciplines:Genetics, Regenerative medicine not elsewhere classified, Stem cell biology